 |
PDBsum entry 2a73
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Immune system
|
PDB id
|
|
|
|
2a73
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structures of complement component c3 provide insights into the function and evolution of immunity.
|
|
|
Authors
|
|
B.J.Janssen,
E.G.Huizinga,
H.C.Raaijmakers,
A.Roos,
M.R.Daha,
K.Nilsson-Ekdahl,
B.Nilsson,
P.Gros.
|
|
|
Ref.
|
|
Nature, 2005,
437,
505-511.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The mammalian complement system is a phylogenetically ancient cascade system
that has a major role in innate and adaptive immunity. Activation of component
C3 (1,641 residues) is central to the three complement pathways and results in
inflammation and elimination of self and non-self targets. Here we present
crystal structures of native C3 and its final major proteolytic fragment C3c.
The structures reveal thirteen domains, nine of which were unpredicted, and
suggest that the proteins of the alpha2-macroglobulin family evolved from a core
of eight homologous domains. A double mechanism prevents hydrolysis of the
thioester group, essential for covalent attachment of activated C3 to target
surfaces. Marked conformational changes in the alpha-chain, including movement
of a critical interaction site through a ring formed by the domains of the
beta-chain, indicate an unprecedented, conformation-dependent mechanism of
activation, regulation and biological function of C3.
|
|
|
|
|
|
|
|
Figure 1.
Figure 1: Structures of human complement components C3 and C3c.
a, b, Ribbon representation of native C3 (13 domains) and C3c
(10 domains), respectively. Also shown are intact thioester (red
spheres), anchor region (grey) and  'NT
(black). c, Domain sequence and arrangements in C3 and C3c. The
colour scheme matches that in a, b. Shown are the thioester site
(white triangle), disulphide bridges, glycan positions (for
details see Supplementary Figs 3 and 6) and cleavage sites.
Sequential proteolysis from C3 to C3c is indicated. d, e,
Intertwined domains. d, MG6 intertwines the  -
and -chain
of mature C3. MG6^  ,
green; MG6^  ,
pink. e, Intertwined CUB. CUB^g, cyan; CUB^f, red.
Fibronectin-type 3 and CUB strand numbering are indicated.
|
|
Figure 5.
Figure 5: The alpha- 'NT
region (residues 727-744) slips through the beta- -ring.
a, Two views, rotated by 180°, of the cone formed by ANA, MG3
and MG8 (surface representation), and residues 730-744 (stick
representation). Residues important for factor B binding are
labelled. b, The 'NT
regions are on opposite sides of the molecule in C3 and C3c. In
C3 this region is covalently linked to ANA; the scissile bond
726-727 is part of a disordered loop 720-729 (dashed line). Also
shown are surface contours of C3 and C3c (transparent light
grey), residues 727-767 (green sticks), ANA and MG6 (ribbons),
and MG2 and MG3 of the -ring
(spheres).
|
|
|
|
|
|
The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2005,
437,
505-511)
copyright 2005.
|
|
|
|
|
|
|
